Multiple sclerosis (MS) is a complex neurological disease characterized by deterioration of central nervous system (CNS) myelin. This insulating material, composed in its majority by lipids (70% lipids, 30% protein), protects axons and makes possible the saltatory conduction, which speeds axonal electric impulse. Demyelination of axons in chronic MS may result in axon degeneration and neuronal cell death, but more specifically, MS destroys oligodendrocytes, the highly specialized CNS cells that generate and maintain myelin.
Oligodendrocyte precursors (PDGFRα+, NG2-proteoglycan+), the immature oligodendrocytes, are generated in ventral areas of the developing brain from a common glial progenitor, actively migrate and proliferate populating the CNS to finally differentiate to premyelinating oligodendrocytes (O4+). At this maturation point, oligodendrocytes both target and extend myelin sheaths along axons or they die. Less explored has been however, the hypothesis of remyelination by either endogenous oligodendrocyte precursors or transplanted cells.
Oligodendrocyte progenitor cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate. Promoting remyelination by inducing differentiation and/or maturation of endogenous oligodendrocyte progenitors can stimulate and enhance intrinsic, natural remyelination thus reduction of clinical severity of myelination related disorders. Therefore, there is a need for compounds and therapeutic methods capable inducing endogenous oligodendrocyte precursor differentiation.